Behavioral impact of neurotransmitter-activated G-protein-coupled receptors: muscarinic and GABAB receptors regulate Caenorhabditis elegans locomotion.
Behavioral impact of neurotransmitter-activated G-protein-coupled receptors: muscarinic and GABAB receptors regulate Caenorhabditis elegans locomotion.
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DOI：
10.1523/jneurosci.0378-08.2008
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发表时间：
2008-07-09
期刊：
影响因子：
--
通讯作者：
Kaplan JM
中科院分区：
文献类型：
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作者：
Dittman JS;Kaplan JM
突触前末梢释放的神经递质激活配体门控离子通道（离子型受体）和多种G蛋白偶联受体（GPCR）。这些神经递质受体在突触前和突触后细胞上都表达。因此，每种神经递质作用于多种受体类别，产生大量的生理反应。许多离子型受体对神经元活动和行为的影响已经清楚地阐明;然而，关于神经递质门控GPCR如何调节神经元和电路的知之甚少。in C.在线虫中，乙酰胆碱（ACh）和GABA都在神经索中释放，并在运动过程中介导快速的神经肌肉兴奋和抑制。在这里，我们确定了毒蕈碱受体（GAR-2）和GABAB受体二聚体（GBB-1/2），分别检测突触释放的乙酰胆碱和GABA。GAR-2和GBB-1/2在ACh和GABA水平升高时抑制胆碱能运动神经元。GPCR的缺失导致运动缺陷，表明这些受体在运动过程中被激活。当GAR-2提供的负反馈被正反馈取代时，动物对ACh水平变得高度敏感，运动严重受损。因此，保守的GPCR在线虫运动回路中起作用，以提供负反馈并调节作为导航基础的运动行为。
Neurotransmitter released from presynaptic terminals activates both ligand-gated ion channels (ionotropic receptors) and a variety of G protein-coupled receptors (GPCRs). These neurotransmitter receptors are expressed on both pre- and postsynaptic cells. Thus, each neurotransmitter acts on multiple receptor classes, generating a large repertoire of physiological responses. The impact of many ionotropic receptors on neuronal activity and behavior has been clearly elucidated; however, much less is known about how neurotransmitter-gated GPCRs regulate neurons and circuits. In C. elegans, both Acetylcholine (ACh) and GABA are released in the nerve cord and mediate fast neuromuscular excitation and inhibition during locomotion. Here we identify a muscarinic receptor (GAR-2) and the GABAB receptor dimer (GBB-1/2) that detect synaptically released ACh and GABA, respectively. Both GAR-2 and GBB-1/2 inhibited cholinergic motor neurons when ACh and GABA levels were enhanced. Loss of either GPCR resulted in movement defects, suggesting that these receptors are activated during locomotion. When the negative feedback provided by GAR-2 was replaced with positive feedback, animals became highly sensitive to ACh levels and locomotion was severely impaired. Thus, conserved GPCRs act in the nematode motor circuit to provide negative feedback and to regulate locomotory behaviors that underlie navigation.